Interpretive Summary: Diet has been shown to play an important role in the development of type 2 diabetes mellitus and the diets commonly consumed in the United States and other developed countries appear to increase the incidence of diabetes. For the majority of the world population, drug treatment for diabetes is not feasible and alternative treatments need to be evaluated. Previous studies suggest that compounds from cinnamon exhibit insulin-like activity in cells, intact animals and people with type 2 diabetes. To understand the molecular basis of the insulin-like activity and explore additional benefits of cinnamon, we investigated the effects of compounds from cinnamon on the utilization of sugar and control of insulin function. Our results show that factors from cinnamon improve compounds that control sugar entry into cells and also inhibit factors involved in inflammation. These results suggest that compounds from cinnamon are involved in the use of sugar by cells and may have additional roles as anti-inflammatory agents. These findings should be of interest to the millions of people with glucose intolerance or diabetes, medical personnel and the lay public.

Technical Abstract:
Dietary factors are involved in the regulation and prevention of type 2 diabetes mellitus. We have shown that cinnamon improves glucose and lipid profiles of people with type 2 diabetes and that a water-soluble cinnamon extract and HPLC-purified cinnamon polyphenols (CP) display insulin-like activity. The objective of this study was to investigate the biochemical basis for the insulin-like effects of cinnamon. Immunoblotting procedure was employed to analyze three proteins, insulin receptor (IR), glucose transporter 4 (GLUT4), and the anti-inflammatory protein tristetraprolin (TTP) involved in insulin signal transduction pathway in mouse 3T3-L1 adipocytes. The results showed that both insulin and CP increased the levels of the three proteins, and recombinant TTP was phosphorylated in vitro by glycogen synthase kinase 3 beta and protein kinases A, B, and C. These results suggest that like insulin, CP increase the amount of the three critically important proteins involved in insulin signaling, glucose transport and inflammatory response. A model of actions was proposed to link CP and TTP in insulin signal transduction pathway. This study provides new biochemical evidence for the beneficial effects of CP in insulin-like action and suggests anti-inflammatory properties of CP.